DE3343532A1 - SUBSTITUTED 5-CYCLOALKYL-2,2-DIMETHYL-PENTAN-3-ONE - Google Patents

Description

BAYER AKTIENGESELLSCHAFT 5090 Leverkusen, Bayerwerk

Central area q _n u

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Substituted 5-cycloalkyl-2,2-dimethylpentan-3-ones

The present invention relates to new substituted 5-cycloalkyl-2,2-dimethyl-pentan-3-ones, a process for their production and their use as intermediates for the synthesis of substances with plant growth regulators and fungicidal effectiveness.

It has already become known that azolyl methyl ketones are used as intermediates for the preparation of azolyl derivatives can be used with plant growth regulating and fungicidal properties (see EP-PS 0 032 200 and EP-PS 0 031 911). For example, by reacting 1- (1,2,4-triazol-1-yl) -3,3-bis-fluoromethyl-butan-2-one with cyclohexyl methyl bromide 1-cyclohexyl-2- (1,2,4-triazol-1-yl) -4,4-bis-fluoromethyl-pentan-3-one can be synthesized according to the following scheme:

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BATH ORIGINAL

O CH ₂ F

CH ₂ -CC

-CH ^ -Br

-HBr

O CH ₀ F

-CH ₉ -CH-CC-

N-

CH ₂ F

However, a disadvantage "that in this type of preparation of azolyl-derivatives having plant growth regulating and fungicidal activity the required as intermediates Äzolyl methyl ketones are available only by multistep syntheses and the materials used as starting materials in part are difficult accessible =

There were now new substituted 5-cycloalkyl-2,2-dimethyl = pentan-3 ~ ones of formula (I)

R-CH ₀ -CH ₀ -CO-C-

CH ₂ Y

in which

(D

represents optionally substituted cycloalkyl,

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X stands for halogen and

Y represents hydrogen or halogen,

found.

It has also been found that the new ones can be substituted 5-Cycloalkyl-2,2-dimethyl-pentan-3-ones of the formula (I) are obtained when ketones of the formulas (Ha, Hb or lic),

CH ₂ X

R ¹ -CH = CH-CO-C-CH ₃ (Ha)

CH ₂ Y

R ¹ -C = C-CO-C-CH ₃

CH ₂ X

C-CH;

CH ₂ Y

or

CH ₂ X

R ² -CH ₂ -CH ₂ -CO-C-CH ₃ (lic) CH ₂ Y

in which

X and Y have the meanings given above,

R for optionally substituted cycloalkyl, optionally substituted cycloalkenyl or optionally substituted aryl, and

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R represents optionally substituted aryl,

selectively with hydrogen in the presence of a hydrogenation catalyst and optionally in the presence of one Reacts diluent.

Finally, it has been found that the new substituted 5-cycloalkyl-2,2 = dimethyl-pentan-3 ~ ones of the formula (I) are very suitable as intermediates for the preparation of 4-azolyl-5-cycloalkyl-2 _p- 2-dimethyl -pentan-3-ones and oils with plant growth regulating and fungicidal effectiveness.

Surprisingly, they can be used to regulate plant growth and fungicidally active 4-azolyl-5-cycloalkyl-2,2-dimethyl-pentan-3-ones and oils based on the substituted 5-cycloalkyl-2,2-dimethylpentan-3-ones according to the invention of formula (I) easier and in higher yield than by the previously known process, in which the corresponding 4-azolyl-2,2-dimethyl = butane = 3-ones were used as intermediate products »

The substances according to the invention are represented by the formula (I) generally defined »In this formula are preferably

R represents cycloalkyl with 5 to 3 carbon atoms which is optionally mono- to triple, identically or differently substituted by alkyl with 1 to 3 carbon atoms,

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- 4k

X for fluorine or chlorine and

Y stands for hydrogen, fluorine or chlorine.

Compounds of the formula (I) in which are particularly preferred

R represents cyclohexyl which is optionally substituted by methyl;

X stands for fluorine and

Y represents hydrogen or fluorine.

For example, 2,2-bisfluoromethyl-5-phenyl-pent-4-en-3-one is used and hydrogen as starting materials and palladium and ruthenium on activated carbon as catalysts, the course of the reaction can Process according to the invention can be represented by the following equation:

CH ₂ F
·

CH = CH-CO-C-CH ₃
H ₂ F

^b \ = J I Pd-C / Ru-C

H) _CH ₂ -CH ₂ -CO-C-CH ₃
CH ₂ F

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If, for example, 2,2 = bisfluoroethyl-5- (cyclohexen-1-yl) pent-4-yne = 3-one is used and hydrogen as starting materials and Raney nickel as a catalyst, see above can the course of the reaction of the inventive method can be represented by the following equation;

= C-CO-C-CH ₃

CH ₂ F Raney Ni

CH ₂ F

H> -CH2-CH ₂ -C0-C-CH ₃ CH ₂ F

For example, do you use 2 _? 2-Bisfluormethy1-5-phenyl-pentan-5-one and hydrogen as starting materials and ruthenium on activated carbon as catalyst , the course of the reaction of the process according to the invention can be shown by the following equation;

CH ₂ F µ

ι H ₂

CH ₂ -CH ₂ -CO-C-CH ₃

CH ₂ F ^Ru ' ^C

CH ₂ F

(H ^ -CH ₂ -CH ₂ -CO-C-CH ₃

CH ₂ F

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For the implementation of the method according to the invention Ketones to be used as starting materials are given by the formulas (Ha), (lib) and (lic) in general Are defined. In these formulas, R preferably stands for b in each case optionally one to three times, Cycloalkyl having 5 to 3 carbon atoms substituted identically or differently by alkyl 7 carbon atoms, cycloalkenyl with 5 to 7 carbon

2
atoms and phenyl. R preferably represents phenyl which is optionally substituted one to three times, identically or differently by alkyl having 1 to 3 carbon atoms.

The ketones of formula (IIa), (lib) and (lic) are still not known.

The ketones of the formula (Ha) can be prepared by adding butan-2-ones of the formula (III)

CH ₂ X

CH ₃ -CO-C-CH ₃ (HD

CH ₂ Y

in which

X and Y have the meanings given above, with aldehydes of the formula (IV)

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R ¹ ^ -CH = O (IV)

in which

R has the meanings given above,

in the presence of a diluent, such as an alcohol "and in the presence of a base, such as a Älkalihydroxides hydroxide or carbonate, at temperatures between 10 ⁰ C and 80 ⁰ C."

The butan-2 ~ ones of the formula (III) and the aldehydes of Formula (IV) are known compounds in organic chemistry.

The ketones of the formula (lib) can be produced by using acetylene derivatives of the formula (V)

(V) in which

R has the meanings given above with pivalic acid halides of the formula (VI),

CH ₂ X

Hal-CO-C-CH ₃ ( _VI )

CH ₂ Y

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in which

X and Y have the meanings given above and

Hal stands for halogen, preferably chlorine or bromine,

in the presence of Cu (I) ions as a catalyst and in the presence of a diluent, such as toluene or pyridine, and in the presence of a base, such as triethylamine, at temperatures between 2O ⁰ C and 100 ⁰ C.

The acetylene derivatives of the formula (V) and the pivalic acid halides of the formula (VI) are known compounds of organic chemistry.

The ketones of the formula (lic) can be produced by one ketones of the formulas

CH ₂ X

R ² -CH = CH-CO-C-CH_ (lld)

ι -1

CH ₂ -Y

or

R ² -C = C-CO-C-CH ₃ (He)

CH ₂ Y

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in which

2
R, X and Y have the meanings given above,

with hydrogen in the presence of a diluent, such as methanol, and ρ in the presence of a catalyst such as Raney nickel or palladium on carbon under normal pressure or under elevated pressure "xtfie preferably 30 to 40 bar, at temperatures between 20 ⁰ C and 40 ⁰ C. selectively hydrogenated on the double bond or »triple bond»

The process according to the invention is carried out in the liquid phase , preferably in the presence of diluents, using a suspended, pulverulent hydrogenation catalyst. The hydrogenation according to the invention can be carried out batchwise or continuously as a bottom or trickle phase hydrogenation in known hydrogenation reactors, such as autoclaves, autoclave cascades, tubular reactors or circulation reactors.

Inert organic solvents are used as diluents when carrying out the process according to the invention in question, these preferably include alcohols such as methanol, ethanol, isopropanol or ethylene glycol; Ethers, such as diethyl ether, diisopropyl ether, ethylene

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glycol monomethyl ether, ethylene glycol dimethyl ether, dioxane or tetrahydrofuran; saturated hydrocarbons such as n-heptane or cyclohexane; and esters, such as ethyl acetate.

Hydrogenation catalysts suitable for the process according to the invention are, for example, those from Metals and / or compounds of elements of the eighth subgroup of the periodic system of the elements Mendeleev exist or contain them. The metals are ruthenium, rhodium, palladium, platinum and cobalt and nickel and their compounds are preferred. The metal compounds can be, for example, oxides, Act hydroxides and / or oxyhydrates. In addition, the metals copper, vanadium, molybdenum, chromium and / or

1 ^b Manganese, as well as compounds of these metals, must be present.

The hydrogenation catalysts can consist exclusively or predominantly of hydrogen-transferring substances exist, but these can also be applied to carrier materials.

As carrier materials for the hydrogen-transferring Substances come into question, for example: inorganic materials such as kieselguhr, silica, aluminum oxide, Alkali and alkaline earth silicates, aluminum silicates, montmorillonite, zeolites, spinels, dolomite, kaolin, Magnesium silicates, zirconium oxide, zinc oxide, calcium carbonate, Silicon carbide, aluminum phosphate, boron phosphate, asbestos, activated carbon or barium sulfate, but also organic

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niche materials, such as naturally occurring ones or synthetic compounds with high molecular weights such as silk, polyamides? Polystyrenes, cellulose or Polyurethanes »Inorganic carrier materials in powder form are preferred.,

Such supported catalysts may be generally 0.5 to 50 wt _o - related% _p is preferably 1 to 10 wt .-% of the hydrogen-transferring substance "refers to the total mass of the supported catalyst containing. The water-

^The substance-transferring substance can be distributed homogeneously in the support material, but catalysts are preferred in the outer layer or on the surface of which the hydrogen-transferring substance is deposited. The catalysts which can be used in the process according to the invention can be produced and shaped in a known manner (see, for example, Houben-Weyl, Methods of Organic Chemistry, Volume IV, Ic, Part I, pp. 16 to 26, Georg Thieme Verlag , Stuttgart, 1980K

Preferred supported catalysts are ruthenium on carbon, ruthenium on aluminum oxide, rhodium on carbon, rhodium on aluminum oxide, palladium on carbon, palladium on aluminum oxide, palladium on calcium carbonate, palladium on barium sulfate, palladium on silica, platinum on carbon and platinum on aluminum oxide, nickel on kieselguhr, Nickel on aluminum oxide and nickel and palladium on aluminum oxide.

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. 22-

Preferred hydrogenation catalysts which consist exclusively or predominantly of a hydrogen-transferring substance, are for example oxidic catalysts such as palladium oxide, platinum oxide, ruthenium oxide and / or Rhodium oxide / platinum oxide according to Nishimura, furthermore by reducing corresponding metal salts or metal salt mixtures with alkali hydrides, alkali boronates, metal alkyls, hydrazine, formaldehyde, hydrogen or black catalysts that can be produced by electropositive metals, such as palladium / black, platinum / black and Rhodium / black; and skeletal catalysts of the Raney type, such as Raney nickel, Raney cobalt, Raney nickel cobalt, Raney nickel-iron, Raney nickel-copper, Raney nickel-iron-chromium, Raney nickel-palladium and Raney nickel-iron-vanadium.

The selection of one or more of the hydrogenation catalysts mentioned expediently depends on the constitution of the starting ketones to be hydrogenated according to the invention of the formulas (Ha), (lib) and (lic).

If the ketones of the formulas (Ha) and (lib) contain optionally substituted cycloalkenyl radicals as substituent R or substituted or unsubstituted cycloalkyl radicals are to be converted into saturated ones Ketones of the formula (I) those catalysts which contain or consist of nickel and / or palladium, particularly preferred.

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The hydrogenation catalysts are used in the process according to the invention used in such an amount that 0.05 to 2.5, preferably 0.1 to 1 wt .-% hydrogen-transferring Substance based on the total weight of the reaction mixture.

Mixtures of two or more of the hydrogenation catalysts mentioned can also be used to carry out the process according to the invention be used"

The catalytic activity of the hydrogenation catalysts remains when the process according to the invention is carried out generally largely preserved, so that these are discontinuous Working method can be used repeatedly and longer when working continuously Time to stay in use.

The reaction temperatures can be varied over a wide range. In general, one works in the range between O ⁰ C and 150 ⁰ C, preferably between 20 ⁰ C and 120 ⁰ C. For the hydrogenation of aliphatic and / or cycloaliphatic C =C = multiple bonds in the ketones of the formulas (Ha) and (lib ) with the catalysts preferred for this, reaction ^{temperatures in the range from 20 °} C. to 60 ^° C. are particularly preferred, while for the hydrogenation of aryl radicals in the ketones of the formulas (Ha), (Hb) and (lic) with the catalysts preferred for this, temperatures im Range from 6O ⁰ C to 120 ⁰ C are particularly preferred.

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The hydrogenations of the invention are preferred carried out at increased pressure. In general, one works between 1 and 150 bar, preferably at 20 to 120 bar. For the hydrogenation of aliphatic and / or cycloaliphatic C-C multiple bonds in the ketones of the formulas (Ha) and (lib) with the catalysts preferred for this purpose are pressures in the range from 5 to 50 bar particularly preferred, while for the hydrogenation of aryl radicals in the ketones of the formulas (Ha), (lib) and (lic) with the catalysts preferred for this purpose, pressures in the range from 5 to 120 bar are particularly preferred.

The one required for the method according to the invention The reaction time depends on the reaction temperature, the hydrogen partial pressure and the intensity of the mixing of the reaction mixture and of the activity and concentration of the hydrogenation catalyst. In general the required reaction time is in the range from 15 minutes to several hours.

The inventive method can, for example, in the simplest embodiment discontinuously in be carried out as follows: A temperature-controllable autoclave provided with a stirring or mixing device is suitably with a ketone of formula (Ha), (lib) or (lic), the hydrogenation catalyst and charged to the diluent. After the autoclave is vented and then hydrogen up to the desired level Pressure has been applied, the mixture becomes

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with intensive mixing to the selected reaction temperature heated »The course of the reaction can easily be determined by measuring the hydrogen consumption, the is compensated by further hydrogen supply, pursue. The hydrogenation is ended when no more hydrogen is consumed and the amount of hydrogen consumed corresponds approximately to the theoretically required amount of hydrogen =

After the hydrogenation has ended, the reaction mixture is cooled, let down and in a known manner, for example by filtering off the catalyst and distilling off the diluent, worked up.

In a particular embodiment of the invention Implementation is carried out in such a way that, in a first stage, ketones of the formula (Ha) are used as substituents R carry an optionally substituted aryl radical, hydrogenated to corresponding ketones of the formula (lic) which are then hydrogenated in a second stage to give the end products of the formula (I) (cf. also the production examples). It should be emphasized that only the C-C multiple bond hydrogenates with high selectivity while the CO double bond is retained »

As already mentioned, represent the new 5-cycloalkyl-2,2-dimethyl-pentan-3-ones of the formula (I) interesting intermediates for the synthesis of 4-azolyl ~ 5-cycloalkyl-

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'26 -

- yt -

2,2-dimethyl-pentan-3-ones and oils with fungicides and plant growth regulating properties.

Such 4-azolyl-5-cycloalkyl-2,2-dimethyl-pentan-3-ones and oils of the formula (VII)

CH ₂ X

R-CH ₂ -CH-AC-CH ₃

I I (VII)

/ Ns, CH ₂ Y

N ¹

in which

R, X and Y have the meanings given above and

A stands for a keto or the CH (OH) group,

can be prepared by adding 5-cycloalkyl-2,2-dimethylpentan-3-ones of formula (I)

CH ₂ X

R-CH ₂ -CH ₂ -CO-C-CH _{3 (I)}

CH ₂ Y

in which

R, X and Y have the meanings given above,

with chlorine or bromine in the presence of an inert organic solvent such as ether,

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chlorinated or non-chlorinated hydrocarbons, are reacted at room temperature, or with the usual chlorinating agents such as sulfuryl chloride, at 20 ⁰ C to 6O ⁰ C is reacted; then the halogen ketones of the formula (VIII) obtained in this way

CH ₂ X

R-CH ₂ -CH-CO-C-CH _{3 (VIII)}

Z CH ₂ Y

in which

R, X and Y have the meanings given above and

Z stands for chlorine or bromine,

with 1, 2, 4-triazole in the presence of an inert organic solvent, such as acetonitrile, and in the presence of an acid binder, such as potassium carbonate or in the presence of an excess of 1,2,4-triazole. Reacts at temperatures between 60 ⁰ C and 120 ⁰ C;

and then optionally the 4-azolyl-5-cycloalkyl-2 "2-dimethyl-pentan-3-ones obtained in this way Formula (VIIa)

CH ₂ X R-CH ₂ -CH-CO-C-CH ₃

^ iNk _N CH ₂ Y (VIIa)

^{1 1}

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in which

R, X and Y have the meanings given above,

by reaction with complex hydrides, such as sodium borohydride or lithium aluminum hydride, in the presence of a polar organic solvent, such as reducing of an alcohol, at temperatures between O ⁰ C and 3O ⁰ C; or by reaction with aluminum isopropylate in the presence of a diluent, such as isopropanol, reduced at temperatures of 2O ⁰ C to 120 ⁰ C.

The 4-azolyl-5-cycloalkyl-2,2-dimethylpentan-3-ones and oils of the formula (VII) have strong fungicidal and plant growth regulating properties Properties (cf. EP 00 31 and EP 00 32 200).

The preparation and use of the invention Substances emerge from the following examples.

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Manufacturing examples example 1

CH ₂ F

CH ₂ -CH ₂ -CO-C-CH ₃

I (1-1)

CH ₂ F

Process variant 1

1st stage

CVh ₂ -CH ₂ -CO-C-CH ₃ (II-1)

CH ₂ F

A 120 1 stirred autoclave made of stainless steel, the temperature of which can be controlled with the aid of an adjustable thermostat, was used with 30 kg (133.9 moles) of 2,2-bisfluoro-methyl-5-phenyl-pent-4-en-TO 3-one, 60 1 methanol and 0.6 kg Raney nickel charged.

After closing the autoclave and displacing the air with nitrogen, the mixture used was pressurized with hydrogen to a pressure of 30 bar and ^{heated to 30 °} C. with stirring. As soon as this temperature was reached, the hydrogen pressure was increased to 40 bar and depending on the hydrogen -Maintain consumption during the entire reaction time.

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After the hydrogen uptake ended after about 5 hours was, one hour under the aforementioned hydrogenation conditions to complete the reaction stirred further, then cooled to room temperature and let down to normal pressure.

The product solution separated off from the catalyst by filtration was continued directly in the without isolation 2nd stage implemented. The 2,2-bisfluoromethyl-5-phenyl-pentan-3-one obtained has a content of 98% (determined by gas chromatography).

2nd stage

( HV

CH ₂ -CH ₂ -CO-C-CH ₃

A 120 1 stirred autoclave made of stainless steel, which can be tempered with the help of an adjustable thermostat, was with a solution of 29.7 kg (131.4 mol) of 2,2-bisfluoromethyl-5-phenyl-pentan-3-one charged in 60 1 of methanol and 0.72 kg of a 5% ruthenium on activated carbon containing catalyst.

After closing the autoclave and displacing the air with nitrogen, the mixture used with hydrogen was supplied up to a pressure of bar 50 and heated with stirring to 9O ⁰ C. As soon as this temperature

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was reached, the hydrogen pressure was on 100 bar increased and maintained in accordance with the hydrogen consumption during the entire reaction time.

After the hydrogen uptake after about 6 hours had ended, the reaction was completed for a further hour under the aforementioned hydrogenation conditions stirred further, then cooled to room temperature and let down to normal pressure.

The product solution separated from the catalyst by filtration was removed from the methanol in a rotary evaporator freed.

30.3 kg (99.4% of theory) of 2,2-bisfluoromethyl-S-cyclohexyl-pentan-S-one were obtained as an oil with a content of 96% (determined by gas chromatography).

Manufacture of the starting product:

CH ₂ F

/ ^ VKH = CH-CO-C-CH ₃ (II-2)

CH ₂ F

A mixture of 106 x 1 g (1 mole) benzaldehyde, 136.1 g (1 mole) 3,3-bisfluoromethyl-butan-2-one, 300 g methanol and 40 g (1 mol) of sodium hydroxide in 70 g of water was stirred for 3 hours at room temperature. Subsequently was the crystalline product filtered off and dried.

201 ^ 8 g (90% of theory) of 2,2-bisfluoromethyl-5-phenyl-pent-4-en-3 = OB were obtained with a melting point of 45 ° C.

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33A3532

- νί -

Example 2

CH ₂ F

H) -CH ₂ -CH ₂ -CO-C-CH ₃ (1-1)

CH ₂ F

Process variant 2

A 0.7 1 stirred autoclave made of stainless steel, the temperature of which can be controlled with the aid of a controllable thermostat, was used with 112 grams (0.5 moles) of 2,2-bisfluoromethyl-5-phenyl-pent-4-en-3-one 300 ml of methanol, 2.8 g of a catalyst containing 5% palladium on activated carbon and 2.8 g of 5% ruthenium charged on catalyst containing activated carbon.

After closing the autoclave and displacing the air with nitrogen was supplied bar up to a pressure of 30 and heated with stirring to 4O ⁰ C hydrogen. As soon as this temperature was reached, the hydrogen pressure was increased to 50 bar and maintained at this level until the hydrogen uptake had ceased (H ₂ consumption about 0.5 mol in 1.5 hours). The reaction ^{solution was then increased to 70 °} C. and the hydrogen pressure to 100 bar and the hydrogenation was continued under these conditions by continuously pushing in hydrogen up to a pressure of 100 bar (H ₂ consumption approx 1.5 moles in 5 hours).

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After the hydrogen uptake was finished, was on Cooled room temperature and relaxed to normal pressure. The product solution separated from the catalyst by filtration was freed from methanol in a rotary evaporator.

113 g (97.4% of theory) of 2,2-bisfluoromethyl-5-cyclohexyl = pentan-3-one were obtained as an oil with a content of 89% (determined by gas chromatography).

Example 3

CH ₂ P

CH ₂ F

ίο ^ ^H > - ⁽

Process variant 3
left level:

CH ₂ F

^) - CH ₂ -CH ₂ -CO-C-CH ₃ (II-1)

CH ₂ F

A 0.3 1 stirred autoclave made of stainless steel, the temperature of which can be controlled with the aid of an adjustable thermostat, was used with 44.4 g (0.2 mol) of 2,2-bisfluoromethyl-5-phenyl-pent-4-yn-3-one, 170 ml of methanol and 5 g of Raney nickel charged.

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After closing the autoclave and displacing the air with nitrogen, the mixture used was pressurized with hydrogen up to a pressure of 30 bar and heated ^{to 30 ° C. with stirring.} As soon as this temperature was reached, the hydrogen pressure was increased to 50 bar and maintained during the entire reaction time in accordance with the hydrogen consumption.

After the hydrogen uptake ended after about 2 hours was, one hour under the aforementioned hydrogenation conditions to complete the reaction stirred further, then cooled to room temperature and let down to normal pressure.

The product solution separated from the catalyst by filtration was removed from the methanol in a rotary evaporator freed.

44.5 g (98.5% of theory) of 2,2-bisfluoromethyl-5-phenyl-pentan-3-one were obtained as an oil with a content of 96.5% (determined by gas chromatography).

^ y

CH ₂ F

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The implementation proceeds according to the 2nd stage in the process variant 1 .

^fH2F

C-CH
CH ₂ F

10.1 g (0.1 mol) of triethylamine and 1.43 g (0.01 mol) of copper (I) bromide were placed in 30 ml of pyridine under nitrogen. 10.2 g (0.1 mol) of phenylacetylene were added and the mixture was stirred for a further 30 minutes. Thereafter, the reaction mixture was admixed dropwise with 15.6 g (0.1 mol) ei, t ^ -Bisfluormethyl-propionic acid chloride and the temperature was kept there at 6O ⁰ C. was left for 15 hours at this temperature, stirred, cooled, washed with water , dried over sodium sulfate and concentrated in vacuo. The residue was purified by distillation.

This gave 17.3 g (78% of theory) of 2,2-bisfluoromethyl-5-phenyl-pent-4-in-3-one of boiling point 103 ⁰ C to 105 ⁰ C / 0.2 mbar.

Example 4

CH ₂ F

/ h \ ch ₂ -ch ₂ -co-c-ch ₃

^ ' CH ₂ F

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- γι -

Process variant 4

A 0.3 1 stirred autoclave made of stainless steel, which with the help of a adjustable thermostat, was with 24 g (0.106 mol) of 2,2-bisfluoromethyl-5- (cyclohexen-1-yl) -pent-4-yn-3-one, 120 ml of methanol and 5 g of Raney nickel charged.

After closing the autoclave and displacing the air with nitrogen, the mixture used was pressurized with hydrogen up to a pressure of 50 bar and heated ^{to 50 ° C. with stirring.} As soon as this temperature was reached, the hydrogen pressure was increased to 70 bar and maintained during the entire reaction time in accordance with the hydrogen consumption.

After the hydrogen uptake was over, the Completion of the reaction for a further hour under the aforementioned hydrogenation conditions, then cooled to room temperature and let down to normal pressure.

The product solution separated from the catalyst by filtration was freed from methanol on a rotary evaporator.

23.5 g (95.5% of theory) of 2,2-bisfluoromethyl.5-cyclohexylpentan-3-one were obtained as an oil with a content of 88.5 ^s (determined by gas chromatography).

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Manufacture_of_Ausgan2S2 £ oduct

CH ₂ F

^ = C-CO-C-CH ₃ (II-4)

CH ₂ F

10.1 g (0.1 mol) of triethylamine and 1.43 g (0.01 mol) of copper (I) bromide were placed in 30 ml of pyridine under nitrogen. 10.6 g (0.1 mol) of cyclohexen-1-yl-acetylene were added and the mixture was stirred for a further 30 minutes. Thereafter, the reaction mixture was admixed dropwise with 15.6 g (0.1 mol) OC, OC-Bis-fluoromethyl-propionic acid and maintaining the temperature at 70 ⁰ C. was allowed to stir for 15 hours at this temperature, cooled, washed with water , dried over sodium sulfate and concentrated in vacuo. The residue was purified by distillation.

This gave 18.1 g (80% of theory) of 2,2-bisfluoromethyl-5- (cyclohexen-1-yl) pent-4-yn-3-one of boiling point 106 ⁰ C to 109 ° C / 0.3 mbar.

Preparation of 4-azolyl-5-cycloalkyl-2,2-dimethyl-pentan-3-ones of the formula (VII)

Example 5

CH ₂ F

^ H) -CH ₂ -CH-CO-C-CH ₃

CH ₂ F

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li stage

H VCH ₂ -CH-CO-C CH ₃ (VIII-1)

Cl CH ₂ F

232.3 g (1 mol) of 2,2-bisfluoromethyl-5-cyclohexyl-pentan-3-one (Example 1) were heated to 80 ⁰ C and in one hour dropwise with 161.9 g (1.2 mol) of sulfuryl offset. Was left for 5 hours at 8O ⁰ C stirred and then distilled off excess sulfuryl chloride in a vacuum. After cooling to 20 ⁰ C was treated with 500 ml Methylxsobutylketon. The organic solution was washed neutral with water, dried over magnesium sulfate and concentrated in vacuo. The residue was distilled.

252 g (90% of theory) of 2,2-bisfluoromethyl-S-chloro-S-cyclohexyl-pentan-S-one were obtained from the boiling point 118 ° C to 120 ° C / 2.5 mbar.

2nd stage

CH ₀ F

CH ₂ -CH-CO-C

Ο ii

N-

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266.7 g (1 mol) of 2,2-bisfluoromethyl-4-chloro-5-cyclohexylpentan-3-one, 69.1 g (1 mole) 1,2,4-triazole and 165.8 g Potassium carbonate (1.2 mol) in 1000 ml of methyl isobutyl ketone were refluxed for 6 hours. After cooling down was washed neutral with dilute hydrochloric acid and with water. The organic phase was over Magnesium sulfate dried and concentrated in vacuo.

329 g (88% of theory) of 2,2-bisfluoromethyl-5-cyclohexyl-4- (1,2,4-triazol-1-yl) pentan-3-one were obtained from Bre-

20th
ching index n ^ = 1.4933.

Example 6

/ - \ ι ι

{H VCH ₂ -CH-CH-C-CH ₃ ¹ ^ - ⁷ _r L _H C

OH CH ₂ F

ι ι

-CH H ₂ F

299 g (1 mol) of 2,2-bisfluoromethyl-5-cyclohexyl-4- (1,2,4-triazol-1-yl) pentan-3-one (Example 5) were dissolved in 300 ml of methanol and at 0 ⁰ C to 5 ⁰ C with a solution of 13.2 g (0.35 mol) sodium borohydride in 150 ml 0.1 normal aqueous sodium hydroxide solution added dropwise. After a reaction time of 2 hours, the reaction solution was adjusted to a pH of 4 to 5 with dilute aqueous hydrochloric acid. After adding 500 ml of water, the end product crystallized out.

Le A 22 728

After drying in vacuo, 286 g (95% of theory) of 2,2-bisfluoromethyl-S-cyclohexyl-'l- (1,2,4-triazol-1-yl) pentan-3-ol with a melting point of 103 were obtained ⁰ C to 105 ⁰ C.

Comparative example

Preparation of the (1,2,4-triazol-i-yl) derivative of the formula

CH ₂ -CH-CO-C CH

Ν -

[ _{% Ν} CH ₂ F (VII-1)

according to the previously known method.

I.i_stage

O CH ₉ F

Il I ^

CH ₃ -CC CH-

^J , 3

CH ₂ F

In a three-necked flask with stirrer, dropping funnel and Liebig condenser with cooled receiver 400 ml of tetraethylene glycol and 46.4 g of potassium fluoride (0.8 mole) were charged and heated to 170 ⁰ C. A water jet vacuum (pressure approx. 20 to 30 mbar) was applied to the inlet of the Liebig condenser. Then, within 45 minutes, 57.6 g (0.2 mol) of 2-acetyl-2-methyl-propane-1,3-diol bismethanesulfate, dissolved in 100 ml of tetraethylene glycol,

Le A 22 728

334353

- 3 / i -

added dropwise. The resulting 3,3-bisfluoromethyl-butan-2-one was distilled off into the cooled receiver during the reaction. After the dropping was another 1 hour at 175 ° C further distilled. The distillate collected was then redistilled. 14 g were obtained (51.5% of theory) 3,3-bisfluoromethylbutan-2-one from Bp. 43 to 46 ° C / 12 mbar.

2nd stage

0 CH ₀ F

Il I * ■

Br-CH ₂ -CG

136 g (1 mol) of 3,3-bisfluoromethylbutan-2-one in 700 ml Methylene laride were added dropwise so with 51 ml (1 mol) Bromine added that discoloration occurred continuously. The solvent was then distilled off in a water jet vacuum. Almost quantitative crude 3,3-bisfluoromethyl-1-bromobutan-2-one was obtained as an oil that could be further converted directly.

3rd stage

V- / V_ «fX λ S.

CH ₂ -CC CH ₃

Le A 22 728

BATH ORIGINAL

215 g (1 mol) of crude 3,3-bisfluoromethyl-i-bromobutan-2-one were converted to 84 g (1.2 mol) of 1,2,4-triazole and 165 g (1 , 2 mol) of ground potassium carbonate in 1 1 of ethanol was added dropwise. The mixture was stirred overnight at 40 ⁰ C, then filtered to remove undissolved material and the filtrate was concentrated. The oily residue was extracted with methylene chloride and water, dried over sodium sulfate and concentrated. The residue was taken up in methylene chloride and 140 ml of ethereal hydrochloric acid were added. The resulting crystalline product was filtered off with suction, extracted with 1 l of methylene chloride and 1 l of saturated aqueous sodium hydrogen carbonate solution, washed with 1 liter of water, dried over sodium sulfate and concentrated. 73.8 g (36.4% of theory) of 3,3-bisfluoromethyl-1- (1,2,4-triazol-1-yl) butan-2-one were obtained as an oil which could be further reacted directly .

4th stage

(H V-CH ₉ -CH-CC

\ _y ^A.

O CH ₂ F

CH ₂ F

A solution of 101.4 g (1.81 mol) of potassium hydroxide in 217.2 ml of water was added at room temperature with stirring to a solution of 369.4 g (1.81 mol) of 2,2-bis-fluoromethyl-4- ( 1,2,4-triazol-1-yl) butan-3-one in 2 liters of dimethyl sulfoxide. To this mixture 320.5 g (1.81 mol) CyclohexyImethylbromid was added dropwise with stirring, keeping the temperature of the reaction mixture was maintained by cooling between 20 and 40 ⁰ C. The Rea-

Le A 22 728

tion mixture was stirred for a further 15 hours at 60 ° C and then poured into 2 liters of water. The mixture obtained was extracted twice with 1 liter of methylene chloride each time, washed the combined organic phases four times with 2 liters of water each time, dried over sodium sulfate and pulled the Solvent off. The oily product present was taken up in acetone and 326 g of naphthalene-1,5-disulfonic acid were added to the solution. The precipitate that formed was filtered off with suction and poured into 2 liters Methylene chloride suspended. This suspension was used twice with 2 liters of saturated aqueous sodium hydrogen carbonate solution each shaken. Then the organic phase was washed with 2 liters of water and after drying concentrated over sodium sulfate under reduced pressure.

In this way, 297.5 g (63% of theory) of 2,2-bis-fluoromethyl-5-cyclohexyl-4- (1,2,4-triazol-1-yl) pentan-3-one were obtained in the form of an oil. n ^ ° = 1.4837

Le A 22 728

Claims (7)

-, «» νί ν1 H J ϋ J /. Claims 1.) Substituted 5-cycloalkyl-2,2-dimethyl-pentan-3-ones the formula CH ₂ X R-CH ₉ -CH ₉ -CO-C CH-. (I) CH ₂ Y in which R represents optionally substituted cycloalkyl, X stands for halogen and Y represents hydrogen or halogen. 2. Substituted 5-cycloalkyl-2,2-dimethyl-pentan-3-ones of formula (I) in which R for optionally one to three times, identically or differently through alkyl having 1 to 3 carbon atoms substituted cycloalkyl with 5 to 7 carbon atoms, X stands for fluorine or chlorine and Y represents hydrogen, fluorine or chlorine. Le A 22 728 3. Process for the preparation of substituted 5-cycloalkyl-2,2-dimethyl-pentan-3-ones the formula CH ₀ X R-CH _n -CH ₀ -CO-C CH ₀ ^ 2. CH ₂ Y in which R represents optionally substituted cycloalkyl, X stands for halogen and Y stands for hydrogen or halogen, characterized in that ketones of the formulas CH ₂ XR ¹ -CH = CH-CO-C CH, (Ha) CH ₂ Y CH ₂ X R ¹ -C ^ c -CO-C CH ₃ CH ₂ Y or CH ₂ X R ² -CH ₂ -CH ₂ -CO-C CH ₃ (n _c ) CH ₂ Y Le A 22 728 343532 in which X and Y have the meanings given above, R for optionally substituted cycloalkyl j, optionally substituted cycloalkenyl or optionally substituted Aryl stands and R represents optionally substituted aryl, selectively with hydrogen in the presence of a hydrogenation catalyst and optionally in the presence of one Reacts diluent. 4. Process for the preparation of 4-azolyl-5-cycloalkyl-2,2-dimethyl-pentane-3 -ones and oils of the formula f ¹ TT t ~, ^ r V ^ -ΓΑ « 4L · R-CH ₉ -CH-AC- CH, (VII) N
in which R represents optionally substituted cycloalkyl, X stands for halogen, Y represents hydrogen or halogen and Le A 22 728 A stands for a keto or a -CH (OH) group, characterized in that substituted 5-cycloalkyl-2,2-dimethyl-pentan-3-ones the formula CH ₂ X R-CH ₂ -CH ₂ -CO-C-CH ₃ (I) CH ₂ Y in which R, X and Y have the meanings given above, with chlorine or bromine in the presence of an inert organic solvent, or with chlorinating agents, if appropriate in the presence of a diluent converts, then the resulting haloketones of the formula CH ₂ X R-CH ₉ -CH-CO-C-CH, (VIII) Z CH ₂ Y in which R, X and Y have the meanings given above and Z stands for chlorine or bromine, Le A 22 728 / 9 - is reacted with 1, 21 4-triazole in the presence of an inert organic solvent, and then optionally the so obtained 4-azolyl-5-cycloalkyl-2,2-dimethylpentane = 3 = one of the formula CH ₉ X
« * · R-CH ₀ -CH-CO-C CH-. W ^ _n CH ₂ Y (VIIa) N 1 in which R, X and Υ have the meanings given above, either with complex hydrides in the presence of a polar organic solvent, or with aluminum isopropylate reacts in the presence of a diluent » 5. Formula ketones R ¹ -CH = CH-CO-C-CHo CH ₂ Y in which R for optionally substituted cycloalkyl, optionally substituted cycloalkenyl or optionally substituted aryl. Le A 22 728 X represents halogen and Y represents hydrogen or halogen. 6. Process for the preparation of ketones of the formula CH ₂ X R ¹ -CH = CH-CO-C-CH ₃ (Ha) CH ₂ Y in which R for optionally substituted cycloalkyl, optionally substituted cycloalkenyl or optionally substituted aryl, X represents halogen and Y represents hydrogen or halogen, characterized in that butan-2-ones of the formula CH ₂ X CH ₃ -CO-C-CH ₃ (III) CH ₂ Y in which X and Y have the meanings given above, Le A 22 728 with aldehydes of the formula R ¹ -CH = O (IV) in which R has the meanings given above, reacts in the presence of a diluent and in the presence of a base » 7. Formula ketones (lic) in which TO R for optionally substituted aryl stands, X stands for halogen and Y stands for hydrogen or halogen, ο a process for the preparation of ketones of the formula Le A 22 728 R ² -CH ₂ -CH ₂ -CO-C-CH ₃ (lic) CH ₂ Y in which R represents optionally substituted aryl, X represents halogen and Y represents hydrogen or halogen, characterized in that one ketones of the formulas CH ₂ X R ² -CH = CH-CO-C-CH ₃ (lld) CH ₂ Y or CH ₂ X R ² -C = C-CO-C-CH ₃ (He) CH ₂ Y in which R ² , X and Y have the meanings given above, Le A 22 728 with hydrogen in the presence of a diluent and in the presence of a catalyst ο Le A 22 728